Prostaglandin D.sub.2 (PGD.sub.2) is synthesized in a number of tissues including brain, spleen, lung, mast cells, bone marrow, stomach, skin and eye (Negishi M., et al., Prog. Lipid Res. 32:417-434, 1993, and references within). Central nervous system actions of PGD.sub.2 are thought to involve effects on sleep induction, body temperature, olfactory function, hormone release, inflammation and analgesia (Negishi M., et al., supra, and references within). PGD.sub.2 can cause inhibition of platelet aggregation (Coleman R. A., et al., Pharmacological Reviews 46:205-229, 1994, and references within). PGD.sub.2 is also the predominant prostanoid released from mast cells upon immunologic challenge and as such is thought to be a mediator of various allergic disorders including but not limited to allergic rhinitis and airway hyperreactivity (Ito S. et al., Prostaglandins Leukotrienes and Essential Patty Acids. 37:219-234, 1989, and references within). It may also stimulate secretion in the intestine. Topically applied PGD.sub.2 has also been shown to reduce intraoccular pressure (Woodward D. F., et al. European J. Pharmacology. 230:327-333, 1993, and Nakajima M., et al., Graefe's Arch. Clin. Exp. Ophthalmol. 229:411-413, 1991).
The physiological actions of PGD.sub.2 are mediated through interaction with the prostanoid DIP receptor. The DIP receptors are thought to be distributed mainly in blood platelets, smooth muscle of various tissues and nervous tissue, including the central nervous system (Coleman R. A., et al., supra, and references within). However, the DP receptor is the least ubiquitous and least abundant of the prostanoid receptors and as such is the one least well characterized. To further complicate matters many of the actions of PGD.sub.2 and distribution of their receptor are also species dependent. Specific binding sites for the DP receptor have been tentatively studied using human platelet membranes, rat brain synaptic membranes and membranes prepared from a cell line derived from bovine embryonic trachea (Coleman R. A., et al., supra, and references within).
The above methods for studying DP receptor activities have several disadvantages in that most if not all preparations contain several different but related prostanoid receptor populations, each with different ligand binding properties, making measurements of absolute potency and selectivity very unpredictable. In addition, the low abundance of the DP receptor in various tissues or cells makes it very difficult to satisfactorily test for compounds as modulators, effectors, agonists or antagonists, of the human DP receptor.